NRG-CC004 ancillary data study-exploring the effect of bupropion on sexual desire in female cancer survivors with and without vulvovaginal symptoms.

BACKGROUND: Female cancer survivors often experience estrogen-deprivation symptoms, which may lead to decreases in sexual desire, vulvovaginal health (lubrication, dryness, discomfort), and sexual satisfaction. Interventions are needed to address these concerns. AIM: The objective of this secondary analysis was to determine if women with higher (better) scores on the Female Sexual Function Index (FSFI) lubrication and pain subscales reported higher desire scores based on treatment with bupropion vs placebo. METHODS: Participants were part of NRG Oncology's NRG-CC004 (NCT03180294), a randomized placebo-controlled clinical trial evaluating bupropion (150 vs 300 mg) to improve sexual desire in survivors of breast or gynecologic cancer. All participants with baseline data from the FSFI lubrication, pain, and desire subscales with 5- and/or 9-week data were analyzed. The FSFI subscale scores were correlated using Spearman correlation coefficients. Logistic regression was used to determine associations between FSFI desire and other FSFI subscales while accounting for treatment arm and other covariates. OUTCOMES: The primary outcome of NRG Oncology's NRG-CC004 (NCT03180294) randomized phase II dose-finding trial was change from baseline to 9 weeks on the FSFI desire subscale score. Similar to the parent study, the primary outcome for this ancillary data study was the FSFI desire subscale score at 5 and 9 weeks. RESULTS: Overall, 230 participants completed the FSFI at baseline and 189 at 9 weeks. The strongest correlations were between lubrication and pain at baseline (all participants, rho = 0.77; bupropion arms, rho = 0.82), week 5 (all participants, rho = 0.71; bupropion arms, rho = 0.68), and week 9 (all participants, rho = 0.75; bupropion arms, rho = 0.78), and the weakest correlations were between desire and pain. In patients in the treatment arms there were no interactions between lubrication or pain.The impact of various covariates on the FSFI score for desire at 9 weeks demonstrated that participants of non-White race (odds ratio [OR], 0.42; 95% CI, 0.21-0.81; P = .010), with a high lubrication score (OR, 0.36; 95% CI, 0.21-0.61; P = .0002), with a high pain score (less pain) (OR, 0.50; 95% CI, 0.29-0.87; P = .014), or with prior pelvic surgery (OR, 0.38; 95% CI, 0.23-0.63; P = .0002) had lower odds of having low desire. CLINICAL IMPLICATIONS: Acute estrogen-deprivation symptoms should be addressed prior to sexual desire intervention. STRENGTHS AND LIMITATIONS: This secondary analysis was not powered to examine all variables. CONCLUSION: Lubrication and pain were predictors of low desire. Therefore, vulvovaginal atrophy and associated genitourinary symptoms of menopause such as vaginal dryness and dyspareunia should be addressed prior to or in parallel with interventions for sexual desire.

Clinical Utility of Genomic Recurrence Risk Stratification in Early, Hormone-Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Breast Cancer: Real-World Experience.

BACKGROUND: RNA-based genomic risk assessment estimates chemotherapy benefit in patients with hormone-receptor positive (HR+)/Human Epidermal Growth Factor 2-negative (ERBB2-) breast cancer (BC). It is virtually used in all patients with early HR+/ERBB2- BC regardless of clinical recurrence risk. PATIENTS AND METHODS: We conducted a retrospective chart review of adult patients with early-stage (T1-3; N0; M0) HR+/ERBB2- BC who underwent genomic testing using the Oncotype DX (Exact Sciences) 21-genes assay. Clinicopathologic features were collected to assess the clinical recurrence risk, in terms of clinical risk score (CRS) and using a composite risk score of distant recurrence Regan Risk Score (RRS). CRS and RRS were compared to the genomic risk of recurrence (GRS). RESULTS: Between January 2015 and December 2020, 517 patients with early-stage disease underwent genomic testing, and clinical data was available for 501 of them. There was statistically significant concordance between the 3 prognostication methods (P < 0.01). Within patients with low CRS (n = 349), 9.17% had a high GRS, compared to 8.93% in patients with low RRS (n = 280). In patients with grade 1 histology (n = 130), 3.85% had a high GRS and 68.46% had tumors > 1 cm, of whom only 4.49% had a high GRS. Tumor size > 1cm did not associate with a high GRS. CONCLUSION: Genomic testing for patients with grade 1 tumors may be safely omitted, irrespective of size. Our finds call for a better understanding of the need for routine genomic testing in patients with low grade/low clinical risk of recurrence.

Randomized Controlled Phase II Evaluation of Two Dose Levels of Bupropion Versus Placebo for Sexual Desire in Female Cancer Survivors: NRG-CC004.

PURPOSE: Because of the negative impact of cancer treatment on female sexual function, effective treatments are warranted. The purpose of this multisite study was to evaluate the ability of two dose levels of extended-release bupropion, a dopaminergic agent, to improve sexual desire more than placebo at 9 weeks, measured by the desire subscale of the Female Sexual Function Index (FSFI), and to evaluate associated toxicities. METHODS: Postmenopausal women diagnosed with breast or gynecologic cancer and low baseline FSFI desire scores (< 3.3), who had completed definitive cancer therapy, were eligible. Women were randomly assigned to receive 150 mg or 300 mg once daily of extended-release bupropion or a matching placebo. t-tests were performed on the FSFI desire subscale to evaluate whether there was a significantly greater change from baseline to 9 weeks between placebo and each bupropion arm as the primary end point. Sixty-two patients per arm provided 80% power using a one-sided t-test. RESULTS: Two hundred thirty women were randomly assigned from 72 institutions through the NRG Oncology NCORP network. At 9 weeks, there were no statistically significant differences in change of the desire subscale scores between groups; participants in all three arms reported improvement. The mean changes for each arm were placebo 0.62 (standard deviation [SD] = 1.18), 150-mg once daily bupropion 0.64 (SD = 0.95), and 300-mg once daily bupropion 0.60 (SD = 0.89). Total and subscale scores on the FSFI were low throughout the study, indicating dysfunction in all groups. CONCLUSION: Bupropion was not more effective than placebo in improving the desire subscale of the FSFI. Subscale and total scores of the FSFI demonstrated dysfunction throughout the 9 weeks of the study. More research is needed to support sexual function in female cancer survivors.